The ENIGMA Center for Worldwide Medicine, Imaging and Genomics galvanized the brain imaging and genomics communities worldwide to pool all their data, talents, and infrastructure to work on previously intractable computational and biomedical goals. ENIGMA'S Administrative Core offers support, leadership, and democratic policies to create the largest brain imaging genomics studies in history. Our Aims are: Aim 1. Coordinate the largest worldwide genomic analyses of images. The ENIGMA Center and its Support Groups will coordinate work by 287 scientists at 125 institutions. Our expertise, administrative support, and analytical resources will accelerate worldwide studies of the brain across the U.S., Europe, Australia, Asia and Africa. Our Support Groups distribute computations on worldwide genomic, imaging and clinical data, in ever-increasing power and depth. Aim 2. Coordinate Worldwide ENIGMA Working Groups on Disease. ENIGMA coordinates 9 mutually supportive Working Groups on 9 major worldwide brain diseases: schizophrenia, bipolar disorder, major depression, ADHD, OCD, autism, 22q deletion syndrome, HIV/AIDS and addictions. These multinational activities use large-scale distributed computation to draw on massive infrastructure and expertise from 287 scientists from 20 countries. Guiding principles are: clear and unified medical goals, protocol harmonization, consortium science, and meta-analysis to improve disease diagnosis and prognosis worldwide. Aim 3. Implement ethical worldwide collaboration. We will assure ethical handling of biomedical Big Data, authorship, credit, and democracy. We encourage secondary proposals to work with ENIGMA data. Projects use Memoranda of Understanding (MoUs), with clear policies for timelines, embargo handling and conflict resolution. Aim 4. Sustain ENIGMA'S growth. We introduce metrics to evaluate how our ENIGMA Center impacts the scientific community. We synergize with other Big Data efforts, helping with training, and scientific exchange, saving costs. Sustained funding will involve philanthropy and will leverage multi-continent support and our partners' non-US infrastructure.